EFFECTS OF THE NEUROPEPTIDE, SUBSTANCE-P, ON LYMPHOCYTE-PROLIFERATIONIN RHEUMATOID-ARTHRITIS

There is evidence supporting the involvement of the neuropeptide, subs tance P, in the pathogenesis of rheumatoid arthritis. In view of the s uggested role of T-cells in this disease, we have investigated the eff ects of substance P on mitogen-induced lymphocyte proliferation in rhe umatoid arthritis patients. The peripheral blood mononuclear cells fro m 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10(-10) M to 10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [H-3 ]thymidine incorporation into the cells. Substance P enhanced, in a do se-dependent manner, the lymphocyte proliferative responses both in rh eumatoid arthritis patients and in controls. Although there was a tren d towards a greater enhancing effect in the rheumatoid arthritis patie nts, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferat ion with substance P that were clearly outside the range seen in healt hy controls. The possibility that substance P has a role in the pathog enesis of rheumatoid arthritis through the upregulation of lymphocyte activation should be considered in further studies of the immunomodula tory properties of substance P in arthritis.